The long-term goal of this project is to identify some of the mechanisms that are responsible for brain amino acid uptake, particularly those that are active at the blood-brain barrier and at the barrier between the blood and cerebrospinal fluid. The project is mainly directed towards the exploration of the role of glutathione in the functioning of transport processes. The amino acid uptake of isolated brain capillaries and of the choroid plexus will be determined. The specificity of the uptake and the requirements for the transport will be studied. The relationship of qlutathione to transport will be studied by determining the uptake capacity of preparations that were depleted in intracellular glutathione by the administration of inhibitors of biosynthesis of this tripeptide. Studies are being pursued on the mechanism of convulsive action of allylglycine and the potent inhibition of brain glutamate decarboxylase by 2-keto-4-pentenoic acid, an allylglycine derived metabolite. The enzyme profile of brain microvessels is also under investigation.